Twelve-Month Outcomes for Remitters Following Electroconvulsive Therapy for Depression

J Clin Psychiatry 2022;83(3):21lr14371

To cite: Jelovac A, McLoughlin DM. Twelve-month outcomes for remitters following electroconvulsive therapy for depression. J Clin Psychiatry. 2022;83(3):21lr14371.
To share: https://doi.org/10.4088/JCP.21lr14371

© Copyright 2022 Physicians Postgraduate Press, Inc

^aDepartment of Psychiatry, Trinity College Dublin, St Patrick’s University Hospital, Dublin, Ireland
^bTrinity College Institute of Neuroscience, Dublin, Ireland
*Corresponding author: Declan M. McLoughlin, PhD, Department of Psychiatry, Trinity College Dublin, St Patrick’s University Hospital, James St, Dublin D08 K7YW, Ireland (d.mcloughlin@tcd.ie).

See reply by Andrade and article by Andrade

To the Editor: We thank Dr Andrade¹ for his interest in our work.² What he describes as an observational study was in fact an analysis of 12-month relapse from a randomized trial of unilateral vs bilateral electroconvulsive therapy (ECT) for depression, ie, a planned secondary outcome of an interventional study. The hypothesis underlying the trial was noninferiority of right unilateral versus bitemporal ECT.³ Randomization and blinding were preserved throughout the follow-up period. In this secondary analysis, we examined long-term outcomes because it could be argued that although acute outcomes were similar in the two groups, remission may be more transient in the unilateral group and the advantage of bitemporal ECT would only become apparent later. As such, electrode placement (ie, treatment group) was the main covariate of interest and cannot be dropped from the regression model simply because it turned out not to be “significant.”

Dr Andrade seems to suggest that including a priori known prognostic factors in a regression model is overfitting. On the contrary, this is standard practice. Inclusion of these covariates reduces the amount of residual variance in the model. Choice of covariates is never an easy task, but it is particularly challenging in a situation like this one, in which thousands of clinical and biological datapoints were recorded. Knowing that we would ultimately be faced with a large number of candidate covariates and the danger of observing many (possibly spurious) associations, we limited ourselves to a handful of known prognostic factors found in systematic reviews of the ECT literature and/or large cohort studies of recurrence in treatment-resistant depression in order to avoid overfitting. There is over half a century of prospective research on post-ECT relapse. Several immutable patient and illness characteristics have been shown to predict both acute and long-term ECT outcomes, while ECT technical parameters or the adequacy of post-ECT prophylactic treatment do not moderate long-term outcomes to any clinically meaningful degree, with two known exceptions: lithium⁴ and continuation ECT.⁵

Maximizing the chances of a good long-term outcome, therefore, is largely predicated on careful patient selection, ensuring that ECT is delivered only to those who are suitable candidates for it. For these reasons, second-generation antipsychotics were not analyzed since there is, to our knowledge, no evidence demonstrating their usefulness in mitigating post-ECT relapse. Recent large observational studies from Scandinavia have shown that antipsychotics are associated with worse long-term outcomes after ECT in unipolar⁶ and bipolar depression.⁷ While causality cannot be inferred from these studies, the preliminary evidence is not encouraging. At any rate, the proportion of our remitters maintained on second-generation antipsychotics (mean dose of 8 mg olanzapine equivalents) who relapsed was similar to those treated with other medication classes (Fisher exact P = .599), though this is clearly not a randomized comparison.

All of us working in the ECT field agree that very large multicenter studies are needed. In the meantime, clinical decisions must be made daily based on imperfect data. We therefore should not rule out most of the available evidence on post-ECT relapse.

Published online: April 18, 2022.
Potential conflicts of interest: Dr McLoughlin has received speaker’s honoraria from Mecta and Otsuka and an honorarium from Janssen for participating in an esketamine advisory board meeting. Dr Jelovac reports no conflicts of interest.
Funding/support: This work was supported by awards from the Health Research Board, Ireland (grants TRA/2007/5, HPF/2010/17, and TRA/2007/5/R).